Factors determining degree of inflation in intratracheally fixed rat lungs

1980 ◽  
Vol 48 (2) ◽  
pp. 389-393 ◽  
Author(s):  
G. Hayatdavoudi ◽  
J. D. Crapo ◽  
F. J. Miller ◽  
J. J. O'Neil

The total lung capacity (TLC) of rats was measured in vivo and was compared to the displacement volume of the lungs following intratracheal fixation with glutaraldehyde or formaldehyde solution. When glutaraldehyde was used the speed of infusion of the fixative was an important factor in the final degree of lung inflation achieved. With a low rate of fixative infusion and a final pressure of 20 cm of fixative the glutaraldehyde-fixed lungs inflated to 55% TLC. With a high initial flow of glutaraldehyde and a final pressure of 20 cm of fixative the lungs inflated to 84% TLC. Fixation of lungs inside the intact chest wall was found to result in a higher degree of inflation. With a reservoir height of 20 cm and a low rate of fixative infusion lungs fixed in situ reached 74% TLC, whereas lungs fixed in situ, but from animals that have been exsanguinated prior to fixation, inflated to only 58% TLC. This suggests that the volume of the blood in the lungs prior to infusion of glutaraldehyde influences the degree of inflation achieved. Formaldehyde-fixed lungs required 72 h to be completely fixed and they were inflated to 90% TLC when a reservoir height of 20 cm was used. Because of the slow rate of fixation using with formaldehyde solution the rate of infusion was found not to limit the degree of inflation that could be achieved.

2004 ◽  
Vol 96 (5) ◽  
pp. 1658-1664 ◽  
Author(s):  
Shawn E. Soutiere ◽  
Wayne Mitzner

Maximal lung volume or total lung capacity in experimental animals is dependent on the pressure to which the lungs are inflated. Although 25-30 cmH2O are nominally used for such inflations, mouse pressure-volume (P-V) curves show little flattening on inflation to those pressures. In the present study, we examined P-V relations and mean alveolar chord length in three strains (C3H/HeJ, A/J, and C57BL/6J) at multiple inflation pressures. Mice were anesthetized, and their lungs were degassed in vivo by absorption of 100% O2. P-V curves were then recorded in situ with increasing peak inflation pressure in 10-cmH2O increments up to 90 cmH2O. Lungs were quickly frozen at specific pressures for morphometric analysis. The inflation limbs never showed the appearance of a plateau, with lung volume increasing 40-60% as inflation pressure was increased from 30 to 60 cmH2O. In contrast, parallel flat deflation limbs were always observed, regardless of the inflation pressure, indicating that the presence of a flat deflation curve cannot be used to justify measurement of total lung capacity in mice. Alveolar size increased monotonically with increasing pressure in all strains, and there was no evidence of irreversible lung damage from these inflations to high pressures. These results suggest that the mouse lung never reaches a maximal volume, even up to nonphysiological pressures >80 cmH2O.


1997 ◽  
Vol 82 (2) ◽  
pp. 491-499 ◽  
Author(s):  
Robert H. Brown ◽  
Wayne Mitzner ◽  
Yonca Bulut ◽  
Elizabeth M. Wagner

Brown, Robert H., Wayne Mitzner, Yonca Bulut, and Elizabeth M. Wagner. Effect of lung inflation in vivo on airways with smooth muscle tone or edema. J. Appl. Physiol. 82(2): 491–499, 1997.—Fibrous attachments to the airway wall and a subpleural surrounding pressure can create an external load against which airway smooth muscle must contract. A decrease in this load has been proposed as a possible cause of increased airway narrowing in asthmatic individuals. To study the interaction between the airways and the surrounding lung parenchyma, we investigated the effect of lung inflation on relaxed airways, airways contracted with methacholine, and airways made edematous by infusion of bradykinin into the bronchial artery. Measurements were made in anesthetized sheep by using high-resolution computed tomography to visualize changes in individual airways. During methacholine infusion, airway area was decreased but increased minimally with increases in transpulmonary pressure. Bradykinin infusion caused a 50% increase in airway wall area and a small decrease in airway luminal area. In contrast to airways contracted with methacholine, the luminal area after bradykinin increased substantially with increases in transpulmonary pressure, reaching 99% of the relaxed area at total lung capacity. Thus airway edema by itself did not prevent full distension of the airway at lung volumes approaching total lung capacity. Therefore, we speculate that if a deep inspiration fails to relieve airway narrowing in vivo, this must be a manifestation of airway smooth muscle contraction and not airway wall edema.


1994 ◽  
Vol 76 (2) ◽  
pp. 495-506 ◽  
Author(s):  
A. P. Gauthier ◽  
S. Verbanck ◽  
M. Estenne ◽  
C. Segebarth ◽  
P. T. Macklem ◽  
...  

The ability of the diaphragm to generate pressures at different lung volumes (VLs) in humans may be determined by the following factors: 1) its in vivo three-dimensional shape, radius of curvature, and tension according to Laplace law; 2) the relative degree to which it is apposed to the rib cage (i.e., zone of apposition) and lungs (i.e., diaphragm dome); and 3) its length-force properties. To gain more insight into these factors we have reconstructed from nuclear magnetic images the three-dimensional shape of the diaphragm of four normal subjects under supine relaxed conditions at four different VLs: residual volume, functional residual capacity, functional residual capacity plus one-half of the inspiratory capacity, and total lung capacity. Under our experimental conditions the shape of the diaphragm changes substantially in the anteroposterior plane but not in the coronal one. Multivariate regression analysis indicates that the zone of apposition is dependent on both diaphragm shortening and lower rib cage widening with lung inflation, although much more on the first of these two factors. Because of the changes in anteroposterior shape and expansion of the insertional origin at the costal margin with lung inflation, the data therefore suggest that the diaphragm may be more accurately modeled by a “widening piston” (Petroll's model) than a simple “piston in a cylinder” model. A significant portion of the muscular surface is lung apposed, suggesting that diaphragmatic force has radial vectors in the dome and vectors along the body axis in the zone of apposition. The muscular surface area of the diaphragm decreased linearly by approximately 41% with VL from residual volume to total lung capacity. Diaphragmatic fibers may shorten under physiological conditions more than any other skeletal muscle. The large changes in fiber length combined with limited shape changes with lung inflation suggest that the length-twitch force properties of the diaphragm may be the most important factor for the pressure-generating function of this respiratory muscle in response to bilateral phrenic shocks at different VLs.


Author(s):  
Ynuk Bossé

The deep inspiration (DI) maneuver entices a great deal of interest because of its ability to temporarily ease the flow of air into the lungs. This salutary effect of a DI is proposed to be mediated, at least partially, by momentarily increasing the operating length of airway smooth muscle (ASM). Concerningly, this premise is largely derived from a growing body of in vitro studies investigating the effect of stretching ASM by different magnitudes on its contractility. The relevance of these in vitro findings remains uncertain, as the real range of strains ASM undergoes in vivo during a DI is somewhat elusive. In order to understand the regulation of ASM contractility by a DI and to infer on its putative contribution to the bronchodilator effect of a DI, it is imperative that in vitro studies incorporate levels of strains that are physiologically relevant. This review summarizes the methods that may be used in vivo in humans to estimate the strain experienced by ASM during a DI from functional residual capacity (FRC) to total lung capacity (TLC). The strengths and limitations of each method, as well as the potential confounders, are also discussed. A rough estimated range of ASM strains is provided for the purpose of guiding future in vitro studies that aim at quantifying the regulatory effect of DI on ASM contractility. However, it is emphasized that, owing to the many limitations and confounders, more studies will be needed to reach conclusive statements.


1978 ◽  
Vol 45 (6) ◽  
pp. 957-961 ◽  
Author(s):  
J. M. Drazen ◽  
S. H. Loring ◽  
C. Venugopalan

The effects of intravenous antigen infusion on lung volumes and quasi-static deflationary pulmonary compliance in guinea pigs previously sensitized to ovalbumin were studied in vivo. Ovalbumin infusion significantly increased minimal gas volume to a similar extent in animals with intact or cut vagi. Total lung capacity fell only in animals with intact vagi. Quasi-static compliance fell in both groups of animals, but the fall was significantly greater in animals with intact vagi. These data demonstrate that immediate hypersensitivity reactions alter lung volumes and the elastic properties of the lung by both vagal dependent and vagal independent mechanisms.


1992 ◽  
Vol 73 (1) ◽  
pp. 151-159 ◽  
Author(s):  
D. C. Poole ◽  
O. Mathieu-Costello

To determine the potential range of diaphragm sarcomere lengths in situ and the effect of changes in sarcomere length on capillary and fiber geometry, rat diaphragms were perfusion fixed in situ with glutaraldehyde at different airway pressures and during electrical stimulation. The lengths of thick (1.517 +/- 0.007 microns) and thin (1.194 +/- 0.048 microns) filaments were not different from those established for rat limb muscle. Morphometric techniques were used to determine fiber cross-sectional area, sarcomere length, capillary orientation, and capillary length and surface area per fiber volume. All measurements were referenced to sarcomere length, which averaged 2.88 +/- 0.08 microns at -20 to -25 cmH2O airway pressure (residual volume) and 2.32 +/- 0.05 microns at +20 to +26 cmH2O airway pressure (total lung capacity). The contribution of capillary tortuosity and branching to total capillary length was dependent on sarcomere length and varied from 5 to 22%, consistent with that shown previously for mammalian limb muscles over this range of sarcomere lengths. Capillary length per fiber volume [Jv(c,f)] was significantly greater at residual volume (3,761 +/- 193 mm-2) than at total lung capacity (3,142 +/- 118 mm-2) and correlated with sarcomere length [l; r = 0.628, Jv(c,f) = 876l + 1,156, P less than 0.01; n = 18]. We conclude that the diaphragm is unusual in that the apparent in situ minimal sarcomere length is greater than 2.0 microns.(ABSTRACT TRUNCATED AT 250 WORDS)


1982 ◽  
Vol 52 (4) ◽  
pp. 832-837 ◽  
Author(s):  
A. Vinegar ◽  
E. E. Sinnett ◽  
P. C. Kosch

The ferret, Mustela putorius furo, is a small relatively inexpensive carnivore with minimal housing requirements. Measurements were made from anesthetized tracheotomized supine males. Values obtained during tidal breathing for six animals (576 +/- 12 g) were as follows: tidal volume, 6.06 +/- 0.30 ml; respiratory frequency, 26.7 +/- 3.9 breaths min-1; dynamic lung compliance, 2.48 +/- 0.21 ml cmH2O-1; pulmonary resistance, 22.56 +/- 1.61 cmH2O . l–1 . s. Pressure-volume curves from nine ferrets revealed almost infinitely compliant chest walls so that lung and total respiratory system curves were essentially the same. Total lung capacity (TLC, 89 +/- 5 ml) and functional residual capacity (17.8 +/- 2.0 ml) were determined by gas freeing the lungs in vivo. The TLC of these ferrets is about the same as in 2.5-kg rabbits. Maximum expiratory flow-volume curves showed peak flows of 10.1 vital capacities (VC) . s-1 at 75% VC and flows of 8.4 and 5.4 VC . s-1 at 50 and 25% VC.


2009 ◽  
Vol 364 (1529) ◽  
pp. 2517-2526 ◽  
Author(s):  
Michael Mörschel ◽  
Mathias Dutschmann

Control of the timing of the inspiratory/expiratory (IE) phase transition is a hallmark of respiratory pattern formation. In principle, sensory feedback from pulmonary stretch receptors (Breuer–Hering reflex, BHR) is seen as the major controller for the IE phase transition, while pontine-based control of IE phase transition by both the pontine Kölliker–Fuse nucleus (KF) and parabrachial complex is seen as a secondary or backup mechanism. However, previous studies have shown that the BHR can habituate in vivo . Thus, habituation reduces sensory feedback, so the role of the pons, and specifically the KF, for IE phase transition may increase dramatically. Pontine-mediated control of the IE phase transition is not completely understood. In the present review, we discuss existing models for ponto-medullary interaction that may be involved in the control of inspiratory duration and IE transition. We also present intracellular recordings of pontine respiratory units derived from an in situ intra-arterially perfused brainstem preparation of rats. With the absence of lung inflation, this preparation generates a normal respiratory pattern and many of the recorded pontine units demonstrated phasic respiratory-related activity. The analysis of changes in membrane potentials of pontine respiratory neurons has allowed us to propose a number of pontine-medullary interactions not considered before. The involvement of these putative interactions in pontine-mediated control of IE phase transitions is discussed.


1981 ◽  
Vol 50 (5) ◽  
pp. 1079-1086 ◽  
Author(s):  
J. E. Fish ◽  
M. G. Ankin ◽  
J. F. Kelly ◽  
V. I. Peterman

We examined the effects of lung inflation on induced airway obstruction in 14 atopic asthmatic and 14 atopic nonasthmatic subjects. Subjects were challenged with aerosols of methacholine (MCh) and pollen antigen (Ag), and the effects of inflation were assessed with partial ad full flow-volume curves and by comparing airway conductance measurements before and after deep inspiration to total lung capacity (TLC). Whereas bronchoconstriction was transiently abolished or reduced with inspiration in nonasthmatics, these effects were absent or diminished in asthmatic subjects. Dissimilarities could not be explained by differences in base-line lung function or degree of obstruction produced. Deep inspiration had a greater effect in reducing airway obstruction produced with MCh than with Ag in nonasthmatics. In addition, atropine pretreatment had no effect on inspiration responses in asthmatics given Ag, suggesting that vagal reflexes were not the cause of an impaired ability to reduce bronchomotor tone by lung inflation. Our findings reveal the existence of an intrinsic means of regulating bronchomotor toe by active changes in lung volume and that such a mechanism is impaired in asthma. We suggest that airway hyperactivity in asthma is perhaps less a reflection of enhanced end-organ responsiveness than a reflection of this impaired capacity.


1975 ◽  
Vol 39 (1) ◽  
pp. 23-29 ◽  
Author(s):  
G. M. Tisi ◽  
V. D. Minh ◽  
P. J. Friedman

We studied four supine dogs that were anesthetized with pentobarbital, intubated, and ventilated with a piston pump. The dimensional response of central (CAW) (greater than 2 mm diam) and peripheral airways (PAW) (smaller than 2 mm diam) to changes in transpulmonary pressure (Ptp) was determined by progressive increments in tidal volume (VT). A specially designed electronics relay circuit permitted this relationship to be obtained for points of no flow during tidal volume breathing: i.e., preinspiration (FRC); end inspiration (FRC + VT). The airways were dusted with powdered tantalum. Six airway divisions were identified: four CAW: trachea, main stem, lobar, segmental; and two PAW: subsegmental, and lobular. AP and lateral roentgenograms were obtained by standard technics and primary magnification (mag factor 2). Airway diameters were plotted as a function of transpulmonary pressure between 3 and 26 cmH2O with the diameter at total lung capacity expressed as 100%. The data show that: 1) there is significant distensibility above 5 cmH2O for all airways from the trachea to the lobular airways; 2) that the pressure-diameter plot is a linear plot for each airway from 3 to 26 cmH2O with R values between 0.846 and 0.957; 3) the peripheral lobular airways are more distensible than the central airways (P smaller than 0.05). We attribute the difference in distensibility of the peripheral lobular airways to their lack of cartilaginous support, and their decreased muscular support when compared to the CAW.


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